The ultimate objective of this Bioengineering Research Partnership is creation of significant advances in the functional effectiveness of medical endoscopy for public health care by enabling the real-time, in situ incorporation of the biophysical micro-imaging of the intrinsic diagnostic properties of tissue in vivo. The fluorescence and second harmonic generation in tissue images by multiphoton microscopy (MPM) without the need for extrinsic labeling are expected to enable effective medical utilization of the capabilities of MPM for in vivo detection and diagnostic recognition of maladies such as cancers, collagen structure damage, and fibrotic disease states, etc., by MPM Endoscopy. MPM Endoscopy will utilize the MPM imaging capabilities discovered and analyzed in biophysical laboratory research, including living preparations, and transgenic model animals displaying various disease states - with validation by histology. MPM was invented and continues to be advanced through associated research programs of the PI and key personnel at Cornell University, and now with Weill Medical College of Cornell University. The first essential aim is development of the data foundation for use in human medicine with MPM images of fresh medical biopsies compared to their appraisal and validation by collaborating pathologists'histology and clinical diagnoses, leading to production of atlases of diagnostic MPM images at Weill Medical's laboratory for eventual dissemination. To accomplish this transition of the MPM tissue imaging capabilities from the laboratory to medical application via MPM endoscopy, a representative cadre of physicians and surgeons at Cornell Weill Medical have assembled to partner in testing and evaluating this capability in their diverse specialties. Simultaneously, an essential aim is development of hyper-miniaturized, reliable MPM endoscopic apparati compatible with the diverse geometries required for various organs of human physiology, which can progress in parallel with more accessible designs for equipping of larger scale endoscopies. Despite published progenitors, instrumentation comprises the major developmental challenge of the program. To accomplish this objective, innovative research by our key personnel with established expertise in ultrafast optics and nanostructure fabrication is invoked to design, fabricate and test potential systems. Biomedical engineering of microscopy components installed in endoscopy apparati is required for testing, ultimately in human MPM Endoscopy applications initially by our collaborating MD's. Finally, technology transfer to commercial manufacturers to provide medical instrument availability is required to achieve the ultimate objective of this: new medical capability.